Correlation analysis of JAK-STAT pathway components on prognosis of patients with prostate cancer.

Janus kinases (JAK)/signal transducers and activator of transcription (STAT) pathway is activated constitutively in prostate cancer (PCa). Despite previous reports implying a role of this pathway in the development of clinical hormone-refractory PCa, the correlation of pathway members with the clinicopathologic features and prognosis of patients with PCa has not been elucidated. To address this problem, pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were evaluated by immunostaining in needle biopsies of the prostate from 202 PCa patients treated by definitive therapy (105 cases) or hormonal therapy (97 cases). The correlation of two protein expression with the clinicopathologic features and the prognosis of PCa were subsequently assessed. The expression levels of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were both positively correlated with Gleason score and clinical stage of patients with PCa. Their expression was also significantly higher in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (both P < 0.001). In all patients, the recurrence-free survival (RFS) rates were significantly higher in those with low pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) expression than that in those with high expression (both P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with lower pJAK-1(Tyr1022/1023) (P < 0.001 and 0.012, respectively) and pSTAT-3(Tyr705) expression (P < 0.001 and 0.015, respectively) were significantly higher than in those with higher expression. Cox multivariate analysis showed that the expression levels of pJAK-1(Tyr1022/1023) (P = 0.002) and pSTAT-3(Tyr705) (P = 0.005) were prognostic factors for PCa in addition to extraprostatic extension (P = 0.026) and Gleason score (P = 0.018). The results of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) immunostainings in needle-biopsy specimens are prognostic factors for PCa.